The effect of istradefylline for Parkinson’s disease: A meta-analysis

Abstract

Adenosine A2A receptor antagonists are an alternative treatment strategy for Parkinson’s disease. Several randomized placebo controlled studies have tested the effect of A2A receptor antagonist istradefylline, and more robust evidence has been acquired. This meta-analysis aimed to provide evidence for its efficacy and safety on patients with Parkinson’s disease. After a systematic literature search, we calculated the pooled standardized mean difference and risk ratio for continuous and dichotomous variables, respectively. Further, sensitivity analyses were performed to confirm the effect estimated by meta-analyses. Publication bias was assessed by funnel plot and deviation of intercept. Six studies satisfied our inclusion criteria. Istradefylline (40 mg/day) decreased off time and improved motor symptoms of Parkinson’s disease in homogeneous studies. Istradefylline at 20 mg/day decreased off time and improved motor symptoms, but heterogeneity was found in the analysis of the former among studies. There was a significant effect of istradefylline on dyskinesia in homogeneous studies. Publication bias, however, was observed in the comparison of dyskinesia. Other adverse events showed no significant difference. The present meta-analysis suggests that istradefylline at 40 mg/day could alleviate off time and motor symptoms derived from Parkinson’s disease. Dyskinesia might be worsened, but publication bias prevents this from being clear.

Safety and effectiveness of istradefylline in patients with Parkinson’s disease: interim analysis of a post-marketing surveillance study in Japan

“…Recently, Sako et al conducted a meta-analysis for the efficacy and safety of istradefylline treatment from randomized placebo-controlled clinical studies of advanced PD patients [31]. The present study provided similar results to the meta-analysis by Sako et al regarding the efficacy and safety of istradefylline, in which the drug reduced off-time and improved motor symptoms evaluated by UPDRS Part III score, and increased the risk of dyskinesia.…”

The Role and Development of the Antagonist of Adenosine A2Ain Parkinson’s Disease

“…The recent meta-analysis (n = 6) suggested that 20 mg of istradefylline improves unified Parkinson's disease ranking scale (UPDRS) III. Meanwhile at 40 mg per day, istradefylline could alleviate off time and motor symptoms derived from Parkinson's disease [38]. Phase 3 study (613 randomized patients), done by Isaacson et al concluded that greater reduction from baseline in total hours off time/day were shown at all-time points for istradefylline 20 and 40 mg/day, compared to placebo.…”

Parkinson's disease therapy with Istradefylline and blood biomarkers of epigenetics

“…[14][15][16][17] The treatment of PD with IST has been covered by the national health insurance system in Japan since 2013 as non-dopaminergic adjunctive therapy to L-DOPA, and this treatment has been shown to exert robust effects on motor dysfunctions in both the off and on periods. 18,19 However, several issues associated with A 2A R antagonists/IST remain unclear in PD patients, such as neuronal protection from the pathological evolution of the disease, preventive effects against dyskinesia evolution, and pharmacological actions for up-regulated A 2A R expression, those have not yet been evaluated in any clinical trials. 20,21 In the present study, we examined the effects of the long-term use of IST as an adjunct to L-DOPA (IST-LD) in clinical practice and assessed blood biomarkers of epigenetics, including the A 2A R-p, A 2A R-m, and DNA methylation of the ADORA2A gene in peripheral blood lymphocytes (PBL).…”